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EPA/690/R-07/029F
Final
9-25-2007
Provisional Peer Reviewed Toxicity Values for
Phosphorus pentoxide
(CASRN 1314-56-3)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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Acronyms and Abbreviations
bw
body weight
cc
cubic centimeters
CD
Caesarean Delivered
CERCLA
Comprehensive Environmental Response, Compensation and Liability Act

of 1980
CNS
central nervous system
cu.m
cubic meter
DWEL
Drinking Water Equivalent Level
FEL
frank-effect level
FIFRA
Federal Insecticide, Fungicide, and Rodenticide Act
g
grams
GI
gastrointestinal
HEC
human equivalent concentration
Hgb
hemoglobin
i.m.
intramuscular
i.p.
intraperitoneal
IRIS
Integrated Risk Information System
IUR
inhalation unit risk
i.v.
intravenous
kg
kilogram
L
liter
LEL
lowest-effect level
LOAEL
lowest-observed-adverse-effect level
LOAEL(ADJ)
LOAEL adjusted to continuous exposure duration
LOAEL(HEC)
LOAEL adjusted for dosimetric differences across species to a human
m
meter
MCL
maximum contaminant level
MCLG
maximum contaminant level goal
MF
modifying factor
mg
milligram
mg/kg
milligrams per kilogram
mg/L
milligrams per liter
MRL
minimal risk level
MTD
maximum tolerated dose
MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-ob served-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-ob served-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
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p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
ppb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
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9-25-2007
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
PHOSPHORUS PENTOXIDE (CASRN 1314-56-3)
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude
that a PPRTV cannot be derived based on inadequate data.
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
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circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System
(IRIS; U.S. EPA, 2007) does not list a chronic RfD, chronic RfC or cancer assessment for
phosphorus pentoxide. Subchronic or chronic RfDs, RfCs or cancer assessments for phosphorus
pentoxide are not listed in the Health Effects Assessment Summary Tables (HEAST; U.S. EPA,
1997) or the Drinking Water Standards and Health Advisories list (U.S. EPA, 2006). The
Chemical Assessments and Related Activities (CARA) list (U.S. EPA, 1991, 1994) does not
include phosphorus pentoxide. No standards for occupational exposure to phosphorus pentoxide
have been established by the American Conference of Governmental Industrial Hygienists
(ACGIH, 2007), the National Institute for Occupational Safety and Health (NIOSH, 2007) or the
Occupational Safety and Health Administration (OSHA, 2007). The Agency for Toxic
Substances and Disease Registry (ATSDR, 2007), the International Agency for Research on
Cancer (IARC, 2007), and the World Health Organization (WHO, 2007) have not published
toxicological reviews on phosphorus pentoxide. A toxicity review on inorganic phosphorus
compounds that included phosphorus pentoxide, was consulted for relevant information (U.S.
EPA, 1989).
Literature searches for studies relevant to the derivation of provisional toxicity values for
phosphorus pentoxide (CASRN 1314-56-3) were conducted in MEDLINE, TOXLINE special,
and DART/ETIC (1960's - July 2007); BIOSIS (August 2000 - July 2007); TSCATS/TSCATS
2, CCRIS, GENETOX, HSDB, and RTECS (not date limited); and Current Contents (February
2007 - July 2007).
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Due to its high affinity for water, phosphorus pentoxide is used as drying agent. It is also
used in the manufacture of other chemicals and surfactants as a catalyst in air blowing of asphalt
and in other applications (U.S. EPA, 1989). Phosphorus pentoxide dissolves in water with great
liberation of heat, forming metaphosphoric acid (HPO3) and then phosphoric acid (H3PO4). The
empirical formula for phosphorus pentoxide is P4O10.
This document has passed the STSC quality review and peer review evaluation indicating
that the quality is consistent with the SOPs and standards of the STSC and is suitable for use by
registered users of the PPRTV system.
REVIEW OF PERTINENT LITERATURE
Human Studies
The only information available regarding human exposure to phosphorus pentoxide is
that from an occupational study conducted by Dutton et al. (1993). The investigators studied
lung function in workers exposed to phosphorus pentoxide, phosphoric acid, fluorides and coal
tar pitch volatiles while refining phosphorus rock to obtain elemental phosphorus. Maximum air
levels measured in the study were 2.23 mg/m3 phosphorus pentoxide, 4.21 mg/m3 fluorides and
1.04 mg/m3 coal tar pitch volatiles; levels of phosphoric acid were not provided. No additional
information regarding exposure levels was reported and sampling and analytical methods were
not discussed. All 131 employees of the refinery underwent annual pulmonary function testing
(4-8 annual determinations). Estimated years of exposure in work area where respiratory irritant
levels exceeded "recommended levels" were used as the exposure index. The years of exposure
ranged from less than 5 to more than 20, with substantial numbers of workers at the higher
durations. The recommended levels were 1 mg/m3 for phosphorus pentoxide, 2.5 mg/m3 for
fluorides and 0.2 mg/m3 for coal tar pitch volatiles. Regression analyses of individual mean
values for percent predicted pulmonary function against years of exposure revealed no
statistically significant reductions in forced vital capacity (FVC), forced expiratory volume in 1
second (FEVi) and forced exploratory flow rate from 25% to 75% of FVC (FEF25-75) for
nonsmokers or former smokers. In smokers, although statistically significant reductions
occurred in all three parameters, these disappeared when adjustment for the effect of smoking
was made. No conclusions regarding phosphorus pentoxide can be drawn from this study.
Animal Studies
No information was located regarding the effects of phosphorus pentoxide in animals
following oral exposure. The only data regarding inhalation exposure to phosphorus pentoxide
are acute toxicity data provided by Ballantyne (1981) in an abstract. The investigator exposed
adult male rats, rabbits, mice and guinea pigs for 1 hour to phosphorus pentoxide smoke (36-
2130 mg/m3), generated by burning red phosphorus in an air stream, followed by a 14-day
observation period. The respective 1-hour LC50 values were 1217, 1689, 271 and 61 mg/m3.
Most deaths occurred during or within 24 hours of exposure. In all species, the respiratory tract
was the target of toxicity. Ballantyne (1981) stated that concentrations (in mg/m3) of phosphorus
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pentoxide not associated with respiratory tract pathology in 14-day survivors were 450 in rats
and rabbits, 111 in mice and <36 in guinea pigs.
FEASIBILITY OF DERIVING PROVISIONAL SUBCHRONIC AND CHRONIC
ORAL p-RfD VALUES FOR PHOSPHORUS PENTOXIDE
There are no oral data for phosphorus pentoxide. White phosphorus smoke, which is
used as a screening smoke by the military, contains phosphorus pentoxide as a major constituent.
There is an RfD for white phosphorus on IRIS (U.S. EPA, 1993). Therefore, white phosphorus
was considered as a potential surrogate for derivation of the RfD. The RfD for white phosphorus
on IRIS is based on critical effects of parturition mortality and forelimb hair loss in a one-
generation reproduction study in rats (Condray, 1985). Little is known regarding the
pharmacokinetics and mechanism of action of orally administered white phosphorus, but the
available data suggest that some of the effects may be due to white phosphorus itself, and that
white phosphorus may be transformed not only to phosphoric acid, but also to phosphine in the
body (ATSDR, 1997). Phosphorus pentoxide would not be expected to undergo transformation
to phosphine in the body. In addition, some of the characteristic effects of white phosphorus
exposure by the inhalation, oral and dermal routes have not been seen in the studies of white
phosphorus smoke, the mixture that contains phosphorus pentoxide. These effects include the
critical effects on which the RfD is based (parturition mortality and forelimb hair loss), fatty
degeneration of the liver, phossy jaw in humans and a particular pattern of bone effects in
developing humans and animals (ATSDR, 1997; U.S. EPA, 1989, 1993). Accordingly,
derivation of an RfD for phosphorus pentoxide by analogy to white phosphorus is not
recommended.
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION p-RfC VALUES FOR PHOSPHORUS PENTOXIDE
The inhalation data available for phosphorus pentoxide are limited to an occupational
study of workers exposed to phosphorus pentoxide, phosphoric acid, fluorides and coal tar pitch
volatiles (Dutton et al., 1993). Pulmonary function tests conducted on the workers several times
a year did not reveal any significant alterations. There is also information on acute lethal
concentrations in four animal species presented in abstract form (Ballantyne, 1981). This
information is inadequate for RfC derivation.
Because the major environmental transformation of phosphorus pentoxide is by
hydrolysis to phosphoric acid, and an RfC for phosphoric acid is available on IRIS, we explored
the possibility of using phosphoric acid as a surrogate chemical for derivation of the RfC.
Phosphorus pentoxide is an extremely hygroscopic substance that is used as a drying agent.
Phosphorus pentoxide reacts readily with water to form phosphoric acid. The reaction with
water is exothermic releasing 70,000 calories (Bayer, 1954). Phosphorus pentoxide will even
extract the elements of water from many other substances themselves considered good
dehydrating agents (i.e., it converts pure HNO3 into N2O5 and H2SO4 into SO3) (Cotton et al.,
1999). The Dutton occupational study suggests that the pentoxide was measured in the
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workplace air. Therefore, we cannot conclude that the inhalation exposure was only the
hydrolysis product, phosphoric acid. In addition, we have no conclusive evidence of complete
and immediate hydrolysis. Due to the highly exothermic nature of the hydrolysis process, at
least part of the toxicity can be a result of this process occurring in the lung. Therefore, we have
no basis for using phosphoric acid as a surrogate for phosphorous pentoxide. Lacking other
relevant studies, development of inhalation toxicity values is precluded.
PROVISIONAL CARCINOGENICITY ASSESSMENT FOR
PHOSPHORUS PENTOXIDE
Weight-of-Evidence Descriptor
There are no data with which to assess the potential carcinogenicity of phosphorus
pentoxide. Under the 2005 Guidelines for Carcinogen Assessment (U.S. EPA, 2005), there is
inadequate information to assess the carcinogenic potential of phosphorus pentoxide.
Quantitative Estimates of Carcinogenic Risk
Derivation of quantitative estimates of cancer risk for phosphorus pentoxide is precluded
by the lack of suitable data.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2007. Threshold Limit
Values for Chemical Substances and Physical Agents and Biological Exposure Indices.
Cincinnati, OH.
Aranyi, C., M.C. Henry, S.C. Vana et al. 1988a. Effects of multiple intermittent inhalation
exposures to red phosphorus/butyl rubber obscurant smokes in Sprague-Dawley rats. Inhalation
Toxicology, Premier Issue, p. 65-78
ATSDR (Agency for Toxic Substances and Disease Registry). 1997. Toxicological Profile for
White Phosphorus. Online, http://www.atsdr.cdc.gov/toxprofiles/tpl03.html
ATSDR (Agency for Toxic Substances and Disease Registry). 2007. Toxicological Profile
Information Sheet. Online, http://www.atsdr.cdc. gov/toxpro2 .html
Ballantyne, B. 1981. Acute inhalation toxicity of phosphorus pentoxide smoke. Toxicologist.
1:140.
Bayer, H.G.A. 1954. Lesions of human bronchial tract caused by incendiary bombs containing
phosphorus. Am. Med. Assoc. Arch. Oto. 59:319-321.
Condray, J.R. 1985. Elemental yellow phosphorus one-generation reproduction study in rats.
IR-82-215; IRDNo. 401-189. Monsanto Company, St. Louis, MO.
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Cotton, F.A., G. Wilkinson, C.A. Murillo et al. (Eds.). 1999. Advanced Inorganic Chemistry.
Chapter 10: The group 15 elements: P, As, Sb, Bi. p. 380-443.
Dutton, C.B., M.J. Pigeon, P.M. Renzi, P.J. Feustel, R.E. Dutton and G.D. Renzi. 1993. Lung
function in workers refining phosphorus rock to obtain elementary phosphorus. J. Occup. Med.
3 5(10): 1028-33.
IARC (International Agency for Research on Cancer). 2007. Search IARC Monographs.
Online, http://monographs.iarc.fr/
NIOSH (National Institute for Occupational Safety and Health). 2007. NIOSH Pocket Guide to
Chemical Hazards. Online. http://www.cdc.gOv/niosh/npg/npgd0000.html#F
OSHA (Occupational Safety and Health Administration). 2007. OSHA Standard 1910.1000
TableZ-1. Part Z, Toxic and Hazardous Substances. Online.
http://www.osha-slc.gov/OshStd data/1910 1000 TABLE Z-l.html
U.S. EPA. 1989. Summary Review of Health Effects Associated with Elemental and Inorganic
Phosphorus Compounds: Health Issue Assessment. Prepared by the Office of Health and
Environmental Assessment for the Office of Air Quality Planning and Standards, Washington,
DC. EPA 600/8-89/072.
U.S. EPA. 1991. Chemical Assessments and Related Activities. Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1993. Integrated Risk Information System (IRIS). IRIS Assessment for White
Phosphorus. Office of Research and Development, National Center for Environmental
Assessment, Washington, DC. Online, http://www.epa.gov/iris/subst/0460.htm
U.S. EPA. 1994. Chemical Assessments and Related Activities. Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1995. Integrated Risk Information System (IRIS). Online. IRIS Assessment for
Phosphoric Acid. Office of Research and Development, National Center for Environmental
Assessment, Washington, DC. Accessed 2007. http://www.epa.gov/iris/subst/0697.htm
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. July
1997. EPA/540/R-97/036. NTIS PB 97-921199.
U.S. EPA. 2005. Guidelines for Carcinogen Risk Assessment. Risk Assessment Forum,
Washington, DC. EPA/630/P-03/001F. Federal Register 70(66): 17765-17817. Online.
http://www.epa.gov/raf
U.S. EPA. 2006. 2006 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. EPA 822-R-06-013. Online.
http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf
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U.S. EPA. 2007. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http://www.epa.gov/iris/
WHO (World Health Organization). 2007. Online Catalogs for the Environmental Criteria
Series. Online, http://www.who.int/dsa/cat98/zehc.htm
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